Rare Pulmonology News

Disease Profile

Spastic paraplegia 4

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

G11.4

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

SPG4; Autosomal dominant spastic paraplegia 4; Familial spastic paraplegia autosomal dominant 2;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Spastic paraplegia 4 (SPG4) is the most common type of hereditary spastic paraplegia (HSP) inherited in an autosomal dominant manner. Disease onset ranges from infancy to older adulthood. SPG4 is characterized by slowly progressive muscle weakness and spasticity (stiff or rigid muscles) in the lower half of the body. In rare cases, individuals may have a more complex form with seizures, ataxia, and dementia. SPG4 is caused by mutations in the SPAST gene.[1][2] Severity of symptoms usually worsens over time, however some individuals remain mildly affected throughout their lives.[3] Medications, such as antispastic drugs and physical therapy may aid in stretching spastic muscles and preventing contractures (fixed tightening of muscles).[1][2]

Symptoms

Signs and symptoms of SPG4 usually become apparent in young adulthood; although symptoms may start as early as one year of age and as late as 76 years. Characteristic symptoms include stiff and rigid muscles (spasticity) and weakness in both of the legs and the lower portion of the body. Additional symptoms are different for every affected individual. Other symptoms may include:[2][1]

  • Decreased ability to sense vibrations in the ankles
  • Exaggerated reflexes (hyperreflexia)
  • Ankle spasms
  • High arches in the feet (pes cavus)
  • Reduced bladder control
  • Ataxia (lack of muscle control)
  • Seizures

Some individuals may also experience a mild decline in cognitive function. This decline does not typically affect daily functioning.[3]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Ankle clonus
Abnormal rhythmic movements of ankle
0011448
Babinski sign
0003487
Brisk reflexes
0001348
Functional motor deficit
0004302
Impaired vibration sensation at ankles
Decreased vibration sense at ankles
Decreased vibration sense in feet

[ more ]

0006938
Leg muscle stiffness
0008969
Lower limb muscle weakness
Lower extremity weakness
Lower limb weakness
Muscle weakness in lower limbs

[ more ]

0007340
Lower limb spasticity
0002061
Urinary urgency
Overactive bladder
0000012
5%-29% of people have these symptoms
Cognitive impairment
Abnormality of cognition
Cognitive abnormality
Cognitive defects
Cognitive deficits
Intellectual impairment
Mental impairment

[ more ]

0100543
Distal amyotrophy
Distal muscle wasting
0003693
Dysarthria
Difficulty articulating speech
0001260
Hyperreflexia in upper limbs
0007350
Pes cavus
High-arched foot
0001761
Urinary bladder sphincter dysfunction
0002839
1%-4% of people have these symptoms
Ataxia
0001251
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Seizure
0001250
Percent of people who have these symptoms is not available through HPO
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness

[ more ]

0000718
Agitation
0000713
Apathy
Lack of feeling, emotion, interest
0000741
Autosomal dominant inheritance
0000006
Degeneration of the lateral corticospinal tracts
0002314
Dementia
Dementia, progressive
Progressive dementia

[ more ]

0000726
Depressivity
Depression
0000716
Disinhibition
0000734
Genetic anticipation
0003743
Hyperreflexia
Increased reflexes
0001347
Impaired vibration sensation in the lower limbs
Decreased lower limb vibratory sense
Decreased vibratory sense in lower limbs
Decreased vibratory sense in the lower extremities
Decreased vibratory sense in the lower limbs
Diminished vibratory sensation in the legs

[ more ]

0002166
Insidious onset
Gradual onset
0003587
Low back pain
0003419
Memory impairment
Forgetfulness
Memory loss
Memory problems
Poor memory

[ more ]

0002354
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Paraplegia
Leg paralysis
0010550
Progressive
Worsens with time
0003676
Spastic gait
Spastic walk
0002064
Spastic paraplegia
0001258
Urinary incontinence
Loss of bladder control
0000020
Variable expressivity
0003828

Treatment

Care for SPG4 is usually managed by a team including a primary care physicianneurologist, genetics professional (geneticist and/or genetic counselor), physical therapistsocial worker, and psychologist. Treatment is focused on alleviating symptoms and may include:[3]

  • Medications for leg spasticity (antispastic drugs)
  • Medications to assist in bladder control (anticholinergic antispasmodic drugs) 
  • Regular physician therapy
  • Botulinum toxin and intrathecal baclofen for severe spasticity 

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Social Networking Websites

    • RareConnect is an online social network for patients and families to connect with one another and share their experience living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders). Click on the link above to view the community for Hereditary spastic paraplegia.

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Spastic paraplegia 4. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
      • The Spastic Paraplegia Foundation, a nonprofit organization supporting spastic paraplegia, offers information on Spastic paraplegia 4

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Spastic paraplegia 4. Click on the link to view a sample search on this topic.

          References

          1. Nance MA. Hereditary Spastic Paraplegia. National Organization for Rare Disorders (NORD). 2017; https://rarediseases.org/rare-diseases/hereditary-spastic-paraplegia/.
          2. Spastic paraplegia 4. Genetics Home Reference. January 2008; https://ghr.nlm.nih.gov/condition/spastic-paraplegia-type-4. Accessed 5/27/2016.
          3. Dürr A, Tallaksen C, Depienne C. Spastic Paraplegia 4. GeneReveiws. Aug 16 2012; https://www.ncbi.nlm.nih.gov/books/NBK1160.

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